Although in the past several decades great strides have been made in the control of pathogenic bacteria by various bacteriostatic chemotherapeutic agents such as the sulfa compounds and various antibiotics, these agents are generally quite specific in their action, being for example active against certain gram-negative or gram-positive bacteria. In addition, the use of these chemotherapeutic agents has resulted in the development of mutant strains of pathogens which are resistant to the known bacteriostats.
Accordingly, the search for new agents active against a broad spectrum of pathogens, and in particular against resistant strains, has continued.
The bacteriostatic chemotherapeutic agents are a well known group of compounds which are active in inhibiting the growth of pathogenic bacteria. Thus, antibiotics such as tetracyclines, chloramphenicol, erythromycin, novobiocin, oleandomycin and lincomycin, and other chemotherapeutic active substances such as nalidixic acid and the sulfa compounds are well known bacteriostats which are active in inhibiting the growth of various pathogenic bacteria. A number of these bacteriostatic agents, for example chloramplenicol, exhibit untoward side effects at the dosage necessary to control infections, and therefore their use has been limited; and it has been found desirable to find ways of reducing the dosages of such antibiotics.
Phosphonomycin, a recently discovered antibiotic, is called (-) (cis-1,2-epoxypropyl)phosphonic acid or (-) (1R, 2S)-1,2-epoxypropylphosphonic acid or the non-proprietary name fosfomycin. This antibiotic, and in particular various derivatives thereof such as salts, labile ester and amide derivatives thereof, are valuable antibiotic substances which are active against various gram-negative and gram-positive pathogens such a Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Staphylococcus and Streptococcus bacteria. Because of their outstanding activity and stability, the salts of phosphonomycin such as those of inorganic as well as organic bases represent preferred forms of the antibiotic. The term "phosphonomycin" as used herein includes not only the free acid but also the various derivatives thereof such as the salts, esters and amides which exhibit antibiotic activity.